Method of preparing polymers analogous to enzymes

ABSTRACT

A non-swellable three-dimensional polymer having a component which is a residue of an optically active compound, which residue is chemically removable from said polymer to leave behind in the physical structure of said polymer a void corresponding to the size and shape of said residue of optically active compound, and a particular steric arrangement of functional groups within the void of said polymer corresponding to the chemical structure of said residue of optically active compound, the original polymer having recurring units of the formulas ##STR1## wherein A, C and D are residues bonded to B of compounds which residues are polymerizable or polycondensable and B is a residue of an optically active compound; a process for preparing such polymer and the form of such polymer containing such void and free of the residue of optically active compounds. Analogously the residue B can be an achiral component, the original polymer having recurring units of the formulas ##STR2## wherein A, C and D are residues bounded to B of compounds which residues are polymerizable or polycondensable and B is a residue of a polyfunctional, achiral compound.

This is a division of application Ser. No. 568,639 filed Apr. 16, 1975,which is a continuation-in-part of Ser. No. 390,824 filed Aug. 23, 1973.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention is directed to preparing polymers containing in thepolymeric structure a residue of an optically active compound whichresidue can be removed from the resultant polymer whereby to providepolymers which in their physical structure have a void or cavitycorresponding to the size and shape of the optically active residueremoved therefrom. The polymers containing functional groups in adefinite three-dimensional arrangement externally at their boundarysurface are in cavities.

Such polymers can be used in the shape and size selective absorption ofoptically active antipodes and in specific interactions through thefunctional groups with those of the optically active antipodes, i.e., inthe racemization of racemates into their optically active forms. Thisinvention is also directed to the use of such new polymeric formscontaining a void of size and shape corresponding to an optically activechemical compound for the racemization of racemates. This invention alsoincludes polymers prepared with the use of a polyfunctional, achiralmatrix molecule, that can be removed from the polymer, whereby toprovide polymers containing functional groups in a definite threedimensional arrangement in cavities. They can be used in specificadsorption and interaction with molecules, whose residues and functionalgroups correspond to the size and shape of the void and to thefunctional groups therein. In this way it is possible to achieveseparations of otherwise difficulty separable mixtures. The presentinvention can be considered to be directed to a method of preparingpolymers which polymers can be considered to be analogous to enzymes.

2. Discussion of the Prior Art

In enzymes, which are to be considered as biopolymers, the functionalgroups responsible for interaction with a substrate or receptor arelocated at quite different points on the peptide chain of themacromolecule and are brought into spatial proximity only by thespecific folding of the chain. In the transfer of information thesefunctional groups interact with the corresponding parts of a substrateand thus produce the activity of a reaction of this substrate. Since thespatial arrangement of the peptide chain determines the proximity of thefunctional groups, the desired information cannot be transferredbi-dimensionally as is the case in certain hormones, but is performedtridimensionally at those points at which the functional groups in thespace come into proximity.

A number of attempts have been made to produce synthetic enzyme analogsby copolymerizing a plurality of monomers containing differentfunctional groups, thereby obtaining polymers in which the functionalgroups are randomly distributed in space and the proximity of twodifferent groups occurs only on a purely fortuitous basis. Thisimperfect proximity relationship of the functional groups in thesynthetic enzymes prepared hitherto may also be held responsible fortheir comparatively poor catalytic activity, so that these compounds canbe evaluated as enzyme models to no more than a limited degree.

Polymers are also known which contain optically active compounds in themolecule. For example, L-lysine hydrochloride has been polycondensedwith aromatic or aliphatic dicarboxylic acid chlorides to form polymers(cf. J. Pol.Sc. A-1, 9 (1971), pp. 2413 et seq.). In these polymers,however, the optically active substance is permanently built into themacromolecule and cannot be split off from it again. Furthermore, thisprocedure does not assure a steric, three-dimensional proximityrelationship of functional groups.

The following conditions must accordingly be taken into consideration inpreparing polymers analogous to enzymes:

1. The polymer must have several different functional groups.

2. The functional groups must not be randomly distributed in space butmust be in suitable proximity to one another.

3. The proximity of the functional groups should be not onlybidimensional but also tridimensional.

4. The polymer obtained should be able to enter into specificinteraction with substrates.

It is heretofore known that racemates can be resolved into theiroptically active forms. It has also been proposed heretofore to utilizepolymers of optically active groups either in the main chain of thepolymer or grafted onto side chains, or, in the case of acids or bases,bonded to ion exchangers by means of electrostatic interactions. Thesepolymers have been used to resolve racemates into their opticaly activeforms. The best effects which have been achieved with polymerscontaining grafted chiral groups. However, the resolving factor in theresolution of DL-mandelic acid on chloromethylated polystyrene graftedwith optically active amines was only 1.004 (See Journal of OrganicChemistry, Vol. 31, p. 561 (1966)).

It therefore became desirable to provide an effective means for theresolution of optically active compounds utilizing polymers. Moreespecially, it became desirable to provide a size and shape selectivemolecular absorbent which would preferentially interact with oneoptically active form of a given compound from its opposed rotatoryform. For instance, it became desirable to provide a sized and shapedmolecular absorbent which would preferentially absorb a dextro or levorotatory form in preference to the other optically active form, i.e.,the remaining optical isomer.

SUMMARY OF THE INVENTION

The long felt desideratum in the art has been fulfilled by athree-dimensional non-swellable polymer material comprising a polymer ofan olefinic unsaturated compound or polycondensation polymer orpolyaddition polymer having in its physical configuration, a void whosesize and shape correspond to the size and shape of an optically activecompound and which functional groups have a particular stericarrangement within the void, said polymer material being operative topreferentially absorb and interact with the residue of an opticallyactive compound whose residue and functional groups correspond to thesize and shape of the void and to the functional groups in theconfiguration of the polymer when a racemate thereof is passed over thepolymer material.

Also, in accordance with this invention, there is provided a polymerwhich is an intermediate to the polymer containing the specified sizedand shaped void and the functional groups. The primary polymer is anon-swellable, three-dimensional polymer having a component which is aresidue of an optically active compound which residue is chemicallyremovable from said polymer to leave behind in the physical structure ofsaid polymer a void corresponding to the size and shape of said residueof optically active compound, said polymer having recurring units of theformula ##STR3## wherein A is a residue bonded to B of a compound whichresidue is polymerizable or polycondensable and B is a residue of anoptically active compound.

The present invention further contemplates a method of preparing suchprimary polymer which comprises heating a monomer of A-B at atemperature sufficient to effect polymerization of A while the Bcomponent remains bonded thereto for a period of time sufficient toeffect the polymerization to a polymer having at least two repeatingunits.

By such process, there is produced the above-described non-swellable,three-dimensional polymer having the residue of an optically activecompound therein. This residue of optically active compound can beconsidered as a matrix for due to its specific molecular geometry andthe position of its functional groups in turn determining its opticalbehavior, the residue serves as a directing medium which affects thephysical geometry of the polymer so prepared. Thus, when this residue ormatrix is removed the physical components of the polymer remainphysically oriented as if the residue of optically active material werestill present therein. Thus the void that remains when the residue isremoved conforms to the size and shape of the so-removed residue. Inother words, the polymer structure does not undergo substantiallyphysical change upon removing of the optically active residue.

Such polymer, in its void form, can be employed as a size and shapeselective molecular absorbent. For instance, a racemate having anoptically active component corresponding to the size and shape of thevoid can be passed over the non-swellable void containing polymer andthe optical antipode whose size and shape correspond to such void isabsorbed preferentially to leave behind the racemic mixture and theopposite optical isomer.

Polymers of the present invention are initially prepared from a monomeror mixture of monomers wherein one component is an optically activecompound or a residue of such compound. Preferably, this compound is apolyfunctional compound as will be further explained below. The othercomponent of the mixture of monomers is a residue or compound of apolymerizable or polycondensable material. This latter component can bejoined to the residue of optically active forms through a function otherthan the function accounting for its ability to polymerize orpolycondense. When such monomer is subjected to polymerization there isprepared a material wherein the polymeric units are determined by thenature of the polymerizable, polycondensible monomer component.

As indicated above, it is preferred that the optically active form ispolyfunctional. Stated differently, it is desired that the opticallyactive form is bonded to a second, a third or a fourth residue whichresidues are also polymerizable or polycondensable. The bonding of theoptically active form to the additional residues are at a function whichdoes not affect the ability of the second residue to undergopolymerization or polycondensation or polyaddition. Accordingly, thecomponents of the monomer to be polymerized can be thought of as havingthe following generic formulas: ##STR4## wherein A is a residue of acompound which is polymerizable or polycondensable; B is a residue of anoptically active compound; and C, D and E are residues of other (orsecond) compounds which are polymerizable or polycondensable. Such amonomer is polymerized under conditions where there is formed athree-dimensional polymeric structure which can have cavities and can bemacroporous. It will be realized that inasmuch as component B. theresidue of the optically active compound, functions as a matrix, itssubsequent removal from the so-formed polymer will leave behind a voidcorresponding to its physical shape and size. Since component B ispolyfunctional and optically active, the linkages between the A, C, Dand E components are positioned in response to the physical state ofsuch polymeric components. The entire polymer therefore has a removablecore of optically active component. The so-formed polymers therefore areanalogous to enzymes and have a given arrangement of functional groupscontained therein. In other words, there is a particular stericarrangement of functional groups within the polymeric mass dictated bythe size and shape of the optically active component. The polyfunctionalmatrix molecule can also be an achiral one. In this case the monomer tobe polymerized can be thought of as having the above formulas I., II.,III., too, wherein A, C, D and E are residues of compounds which arepolymerizable or polycondensable and B is a residue of an achiral,polyfunctional compound. After the removal of this achiral matrixmolecule from the three dimensional non-swellable polymer of saidmonomers it will leave behind a void corresponding to its physical shapeand size. Within the void there is a particular steric arrangement offunctional groups within the polymeric mass dictated by the size andshape of the achiral polyfunctional component. For example the distanceof two functional groups within the void of the polymer can be varied byvariation of the distance of the function groups in the matrix molecule.

The optically active or achiral monomer contains one or more functionalgroups linked by 1, 2 or more functional groups to polymerizable orpolycondensable compounds. Preferably, the optically active or achiralcompound is joined to the A, C, D and E residues by linkages which canbe easily split to yield to polymer in its optically active or achiralvoid form. Thus, the optically active or achiral compound can be joinedto the polymerizable or polycondensable residues by any one of thefollowing functions: the carboxyl, carbonyl, sulfonic acid, boric acid,phosphonic acid, amino, imino, acylamino, nitro, alkoxy, hydroxy,mercapto, phosphoric acid mono- and diesters, C₁ to C₈ - alkylamino- orammonium-, hydroxyl amino- or hydrazino.

Additionally, the optically active or achiral compound can be joined tothe A, C, D or E functions by bridges such as present in polycyclicaromates, compounds which form a hydrogen bridge, compounds which havedipol interactions, compounds which have electrostatic interactions,compounds which have hydrophobic interactions, compounds which formcomplexes and compounds which contain charge transfer complexes.Examples of these latter types of linkages include the following:Interactions between chinone and hydrochinone, between two or more C₅-to C₂₅ -alkylchains; between tetraalkylammonium bases and carboxylicacids, between the ether-oxygen and carboxylic acids, between amino-,imino- or amido- groups and carbonyl groups, between trinitrobenzene andmethoxybenzene; between two anthracene moieties.

As indicated above, residues A, C, D and E contain functions whichpermit polymerization or polycondensation or polyaddition at suchfunctions. These functions are apart from those involved in the joiningof the residue itself to the optically active or achiral residue.Preferably, the polymerizable compound contains a polymerizable olefindouble bond. It may also, however, contain other polymerizable orpolycondensable groups from which polymers can be prepared such aspolyacrylates, polyesters, polyurethanes, polyamides, phenolic polymerssuch as phenol formaldehyde and urea polymers such as urea formaldehyderesins and derivatives thereof, including derivatives containingfurfural and furfuryl alcohol.

The present invention has a wide variety of components which can beemployed in the preparation of the corresponding polymer. There is setforth herebelow a table showing the types of residues which can beutilized. Although the table shows residues in each column, eachcomponent

                                      TABLE                                       __________________________________________________________________________    A          B          C          D                                            __________________________________________________________________________    sugars                                                                        p-vinyl-phenyl-                                                                          mannitol   p-vinyl-phenyl-                                                                          p-vinyl-phenyl-                              boronic acid          boronic acid                                                                             boronic acid                                 indene-6-boronic                                                                         methyl-d-D-                                                                              indene-6-boronic                                                                         --                                           acid       manno-pyranoside                                                                         acid                                                               (glucose)                                                                     (galactose, etc)                                                   amino acids                                                                   p-vinyl-   phenylalanine                                                                            p-vinyl-   --                                           aniline    (alanine)  benzaldehyde                                                       (tryptophan)                                                       p-vinyl-   tyrosin    p-vinyl-   p-dimethyl-                                  aniline    (serine)   benzaldehyde                                                                             amino-styrol                                            (cystine)                                                          p-vinyl-   dopa       p-vinyl-   indene-6-                                    aniline               benzaldehyde                                                                             boronic acid                                 acids                                                                         acrylamine tartaric acid                                                                            p-vinyl-phenyl-                                                                          acrylamine                                                         boronic acid                                            p-vinyl-   tartaric acid-                                                                           p-vinyl-phenyl-                                                                          dodecene-1                                   aniline    mono-n-octyl-                                                                            boronic acid                                                       ester                                                              salicylic acid                                                                           mandelic acid                                                                            p-hydroxy  formaldehyde*)                                                     aniline                                                 terpens                                                                       O,p-dicyanato-                                                                           borneol    --         ethylenediamine*)                            benzoic acid                                                                  steroids                                                                      2,4-dicyanato-                                                                           oestradiol --         butanediol-1,4,*)                            toluene-6-                       glycerine*)                                  sulfonic acid                                                                 amines                                                                        isophthalic                                                                              α-phenylethyl                                                                      --         ethylenediamine*)                            acid-m-    amine                                                              sulfonic acid                                                                 alkaloids                                                                     p-vinyl-   desmethyl- methacrylic                                                                              --                                                       xx                                                                aniline    cocaine    acid                                                    achiral matrix molecules                                                      p-aminomethyl-                                                                           4,4'-adipic                                                                               p-aminomethyl-                                                                          --                                           styrene    acid       styrene                                                 p-aminomethyl-                                                                           tricarballylic                                                                           p-aminomethyl                                                                            p-aminomethyl                                styrene    acid       styrene    styrene                                      methacrylic                                                                              1,6 hexanediol                                                                           methacrylic                                                                              --                                           acid                  acid                                                    methacrylic                                                                              p-amino-capronic                                                                         p-aminomethyl                                                                            --                                           acid       acid       styrene                                                 __________________________________________________________________________     A = a residue bonded to B of a compound which residue is polymerizable or     polycondensable                                                               B = a residue of an optically active or achiral compound                      C and D = hydrogen or a residue of a group, bonded to B, which residue        contains a polymerizable or polycondensable function                          *) = these components are not bonded to B, but react in poly-condensation     reactions with A or C    in a given column can be joined to any other         component in the adjoining column. Thus the table is not to be read as     implying that only those residues on a single horizontal line can be     joined to residues on the same horizontal line.

Polymerization is effective by charging the monomer or mixture ofmonomers into a vessel and subjecting it to heat until the polymersthereof are formed. Generally speaking, the polymerization is conductedat a temperature between -80° C and 150° C, preferably between 50 and120° C for a period of time between 1 and 200 hours. The selection ofthe temperature and duration of polymerization will depend upon themonomer compounds and the excess and type of polymerization. Thepolymerization can also be conducted at atmospheric pressures, atsubatmospheric pressure and at superatmospheric pressure. The use of aclosed vessel providing autogenous pressure is particularly contemplatedwhen superatmospheric pressures are to be employed. The pressures rangebetween 20 and 140 psi.

Sub-atmospheric pressure would normally be between 5 and 300 Torr. Thepolymers prepared can have a wide range of molecular weights. Generallyspeaking, the molecular weights will be between 20,000 and the molecularweight of three-dimensional cross-linked polymers, preferably above500,000. These molecular weights are determined in accordance with themeasurement of light-scattering in corresponding polarometers. Thepolymers will generally have more than 150 repeating units. In suchconnection it is important to note that if the monomer contains aplurality of polymerizable or polycondensible groups, the resultantpolymer will be, at least to a minor extent, crosslinked.

The polymerization can be carried out in the absence of a catalystmerely by subjecting the reaction mixture to the appropriatepolymerization parameters. If desired, a catalyst can be used such ase.g. in radical polymerization: azoisobutyro nitrile, dibenzoylperoxide, potassium persulfate; cumolhydro peroxide, azoisobutyronitrile photochemically iniated; Fe⁺⁺⁺ and potassium persulfate;in the presence of popcorn polymers; in ionic polymerization: TiCl₄,BF₃, H₂ SO₄, alkalimetals butyllithium, sodium - or potassiumnaphthaline, in insertion polymerization Ziegler-Natta-catalysts, e.g.Al (Et)₃ and TiCl₄ ; initiation by ultrasonic waves, UV-, X- and γ-rays.

Inasmuch as the present invention has as its prime object thepreparation of a non-soluble three-dimensional polymer, it isparticularly desirable to include in the reaction mixture across-linking agent. Particularly contemplated cross-linking agents aree.g. for polymerization: divinylbenzene, butandiol diacrylate, glycoldimethacrylate, glycoldivinyl ethers, adipic acid divinylester,allyl-vinyl ethers, unsaturated polyesters; for polycondensation e.g.glycerine, cyanuric acid, phenol, melamine, trichlorosilane, maleinicacid, hexamethylenetetramine, for polyaddition: 2,4,6 tricyanto toluene,glycerine, sorbitol, ethylene tetramine, X- and γ-ray. Generallyspeaking, the cross-linking agents are employed in an amount between 0.5and 80 weight percent preferably between 25 and 40-wt. percent basedupon the weight of the monomer. Preferably, particularly in the case ofpolymerization in the presence of a cross-linking agent, thepolymerization is effected in the presence of an inert solution. It hasbeen found that a mixture of solvents, one being a good, the other beinga poor solvent for the resulting polymer, ideally functions as an inertsolvent in the polymerization, according to the invention. The followingare particularly contemplated as solvents for the polymerization:acetonitrile, benzene/acetonitrile, ethylacetate/benzene, benzene,cyclohexane/acetonitrile, diethyl ether, diethylether/benzene,dimethylformamide (DMF), DMF/benzene, chlorobenzene, dioxane,chlorobenzene/dioxane, butylacetate, butylacetate/toluene.

After the polymerization, the matrix is to be partially or completelyremovable from the polymer. The removal is performed with known cleavingagents which dissolve the link to the functional groups so that, on theone hand, the optically active or achiral compounds are formed on theother hand the polymers develop which contain the functional radicals atthe points at which the optically active or achiral compound wasdissolved out, these radicals being bound to the polymer in the stericconfiguration predetermined by the matrix. The dissolution of theoptically active or achiral compound from the polymer matrix can beperformed, for example, by hydrolysis with water, by acid bydrolysis,acid alcoholysis, alkaline hydrolysis, hydrogenation, exchange reactionswith low-molecular amines, aldehydes, etc., double-bond cleavage, glycolcleavage, reduction, or oxidation. The particular reaction or reactionschosen depend upon the nature of the linkage to be cleaved. Neutralhydrolysis can be performed using water or mixtures of water with C₁ -to C₈ - alcohols or mixtures of water with acetone or otherwater-soluble solvents at room temperature or at elevated temperaturesranging from 30 to 150° C.

Acid hydrolysis can be employed using a mineral acid or strong organicacid having a pKa of at least 5. Suitable acids include hydrochloric,sulfuric, nitric, phosphoric, trichloroacetic and sulfonic. Acids wouldgenerally be used such that the solution has a pH of below 4 and theacid hydrolysis would be conducted for a period of time of between 30and 5,000 minutes. Acid alcoholysis is performed using alcohol such as aC1 to C8 alcohol, especially methanol, ethanol, normal propanol,isopropanol and butanols. The alcohol would normally contain between 1and 30 weight percent of an acid having a pKa below 5.

The alkaline hydrolysis would be performed for the same period of time,using an alkaline such as sodium hydroxide, potassium hydroxide andammonium hydroxide or other alkaline agent of pKb of below 5. Thesolution will generally have a pH above 9.

Hydrogenation is performed using hydrogen gas or a source of hydrogen,preferably in the presence of a catalyst such as a noble metalcontaining catalyst, particularly a platinum or palladium catalyst. Itis usually performed at an elevated temperature between 50 and 120° Cfor a period of time between 20 and 1,000 minutes.

The exchange reactions may be carried out employing primary, secondaryor tertiary amines, particularly amines of low molecular weight ofaliphatic or aromatic compounds. Particularly contemplated are analineand the primary and secondary amines of C1 to C8 alkanes.

In lieu of the amines of these organic compounds, an aldehyde can beemployed such as propionaldehyde, formaldehyde or acetaldehyde. Themethods for double bond cleavage, glycol cleavage, reduction oroxidation are per se generally known in respect of the cleavage ofnon-steriospecific compounds. For instance, oxidation can be carried outemploying an oxygen-containing salt such as a permanganate, dromate orvanadate or a source of oxygen gas. An oxidaton catalyst is preferablyemployed. This reaction is normally carried out at an elevatedtemperature under pressure. Reduction, on the other hand, is carried oututilizing a reducing agent such as a lithium containing compound.

It is decisively important that the polymer that forms be insoluble orunswellable in most solvents, or that the arrangement of the chains bemade immutable by other measures. The polymer is to permit good accessto as many functiona groups as possible. The polymer is insoluble, orsparingly soluble, at 25° C in the following materials: benzene,acetonotrile, cyclohexane, water, chloroforme, acetone, ethylacetate,toluene, DNF, dimethyl sulfoxide, dioxane, diethyl ethers, glycol, etc.By "insoluble or sparingly soluble" is meant that less than 5%,preferably less than 0.1%, by weight of polymer is soluble in one (1 )liter of solvent as 25° C.

These requirements are extensively fulfilled by constructing the polymerin a macroporous form. For example, by the choice of a suitablebifunctional crosslinking agent it is possible to control the porosityduring the polymerization and obtain suitable cavities in the polymer.Also, the nature of the inert solvent in whose presence thepolymerization takes place, and the quantity thereof and of thecross-linking agent affect the porosity and the non-swellability. Amixture of a good solvent with a poor solvent has proven to be a goodinert solvent for the polymerization reaction.

The porosity of the polymer is desirable so that the greatest possiblepercentage of the matrix molecule will be able to be dissolved out ofthe polymer, and so that the greatest possible number of functionalgroups possibly exercising an enzymatic action will be present in themacromolecule at an easily accessible point.

The majority of pore diameters range from 50-1000 A, preferably from200-400 A as measured by Hg- porosimetry. The specific inner surfacearea as measured by the BET-method ranges from 50-500 m² /g, preferablyfrom 150-250 m² /g. The non-swellability of the polymer is necessary tothe immutability of the spatial fixation of the functional groups in themacromolecule.

The swellability in solvents those shall be used as reaction medium orchromatographic mobile phase with these polymers does not exceed 10%,preferably it is less than 5%. The swellability can easily bemeasureably the volume enlargement of the polymer in calibrated tubesfilled with this solvent or by gravimetric determination of the solventuptake in the appropriate solvent. The glass transition state asmeasured by differential thermal analysis is at temperature considerablyhigher than the temperature, where the polymers are to be used.Preferably it is higher than 100° C.

These bifunctional compounds can be used preferentially as cross-linkingagents which form copolymers with the copolymerizable groups of themolecule linked to the matrix. If possible, the cross-linking agent willhave the same polymerizable groups as the entire monomeric molecule ofthe matrix. Thus, divinylbenzene or glycoldimethacrylate are suitable ascross-linking agents when the monomeric matrix molecule containsolefinic double bonds.

The polymers prepared in accordance with the present invention aresuitable, on the basis of their above-described properties, as catalystswhose mode of action corresponds to that of enzymes. For example,compounds of complex construction, whose synthesis by conventionalmethods is impossible or is possible only at extreme cost, can be madein a simple and stereochemically uniform manner. Their effectiveness, incontrast to enzymes, is fully sustained even in non-aqueous systems andat elevated temperature.

Polymers prepared with optically active matrix molecules in accordancewith the invention can be employed to separate racemates into thecorresponding optically active compounds. The racemate to be separatedcan also serve, in the form of the one optically active form, as amatrix for the preparation of the polymer. The separation can beperformed most simply, for example, by dissolving the racemate in anon-solvent for the polymer, mixing it with the polymer and stirring.The polymer is then removed by filtration, and the opposite opticallyactive form of the matrix remains concentrated in the filtrate.

The other optically active form remaining in the polymer and bound byesterification or electrostatic bond or by a Schiff base or by chargetransfer complex or by hydrophobic interaction or by complex formationcan be dissolved out of the polymer again in the same manner as in thepreparation of the polymer or in some other manner, preferably thebonding to the polymer is of an easy reversible type. Substantiallygreater concentrations along with automatic performance of the proc esscan be achieved by separation in columns. In this manner, too,derivatives of the matrix serving as an optically active compound orcompounds of similar construction can be separated into their opticallyactive forms by means of the polymer prepared with this matrix.

This method of resolving racemates differs from all other known methodsof racemate resolution in that it is based on an entirely novelprinciple: compounds with asymmetrical carbon atoms are not required inthe polymer in the resolving process, and instead the resolution takesplace in cavities which are asymmetrical due to functional groups,steric delimitations or hydrophobic interactions playing an additionalpart. The enrichment of one optically active form can be on onetheoretical plate between 1 and 10 percent. But also the resolvingfactor α that is, the ratio of the distribution coefficients between thepolymer and the solution of the D and L form, which permits a much moreprecise conception of the separating action of a racemate resolvingmethod than data on the concentration, is much higher than in themethods of the prior art. For DL-glyceric acid, for example, theresolving factor was found to be α = 1.036, and for DL-glyceric acidmethyl ester it was found to be α = 1.012, when a polyvinyl compound wasused as the polymer in accordance with the invention. Such polyvinylcompound was prepared by means of D-glyceric acid as the matrix, thelinking of the D-glyceric acid to the vinyl groups having been performedby means of an ##STR5## on the one hand and through a phenylboric acidester group on the other.

The starting products for the polymers of the invention are prepared bymethods of the prior art. If an optically active dihydroxycarboxylicacid is selected, for example, as the matrix, the linking to thepolymerizable compounds can be performed on the one hand through an acidamide grouping--e.g., through reaction with a vinylaniline--and on theother hand through an easily split-off ester grouping--e.g., by reactionwith a substituted boric acid ester such as vinylboroxine. In thefollowing example, to which the invention is not limited, thepreparation of a corresponding polymer is described.

EXAMPLE 1

(1) Preparation of D-glycericacid-(p-vinylanilide)-2,3-O-(p-vinylphenylboronate) as the monomer to bepolymerized.

Preparation of the Monomer

The preparation of this monomer is performed in four steps, setting outfrom D-glyceric acid methyl ester. In the first step, 18 g of this esteris refluxed with 60 ml of acetone and 0.4 g of p-toluenesulfonic acid in800 ml of methylene chloride with a Vigreux column (30 cm) onthe waterseparator untl no more water of reaction is formed. Then the mixture iscooled, carefully washed with a solution of 1 g of potassium hydroxidein 60 ml of water, then washed twice with 50 ml of water each time,dried with potassium carbonate and distilled first at normal pressureand then with a vacuum. 2,3-O-isopropylidene-D-glyceric acid methylester is a colorless, very fluid liquid with a characteristic esterodor. Boiling point at 12 mm: 77° C Yield: 19.8 g (82.5% of the theory);[α]_(D) ²⁰ =+7.95° (c = 1.12; acetone).

Elemental analysis: C₇ H₁₂ O₄ (1602): Calc.: C 52.49; H 7.55; Found: C51.83; H 7.51

In a second step, the 2,3-O-isopropylidene-D-glyceric acid(p-vinylanilide) is prepared from this compound. The procedure is asfollows.

Into a Grignard reagent solution cooled to 0° C and composed of 5.2 g ofmagnesium and 30.2 g of methyl iodide in 100 ml of anhydrous ether asolution of 23.8 g of p-aminostyrene and 0.5 g of tert.-butylcatechol in100 ml of water-free tetrahydrofurane is slowly added, drop by drop,over a period of 20 minutes and a temperature below 10° C. Then themixture is warmed to 45° C and a solution of 16 g of2,3-O-iso-propylidene-D-glyceric acid methyl ester in 100 ml ofanhydrous tetrahydrofurane is dripped in at such a rate that thetemperature does not exceed 45° C. After that it is heated withrefluxing and stirring for another hour on the water bath, cooled, andhydrolyzed by the addition of 100 g of crushed ice, and then enough 2Nhydrochloric acid is added so that the precipitate that has formedbarely dissolves. The organic stratum is separated and the aqueous phaseis extracted twice with ether and the combined extracts, cooled to 0° C,are washed twice with 80 ml of 2N ice-cooled hydrochloric acid eachtime, and once with 80 ml of ice-cooled water. After drying overpotassium carbonate, the solvent is removed by distillation on therotary evaporator, the residue is dissolved in boiling petroleum ether(40°-60° ), and allowed to crystallize first at room temperature andthen at -20°. 2,3-O-isopropylidene-D-glyceric acid-(p-vinylanilide)crystallizes in fine, colorless needles.

M.p. 76°; [α]_(d) ²⁰ = +32°: (c = 1.06; acetone); yield: 20.9 g (89% ofthe theory).

Elemental analysis: C₁₄ H₁₇ NO₃ (247.3) calc.: C 67.99; H 6.93; N 5.66;found: C 67.90; H 6.95;

In the third reaction step the isopropylidene groups are first split offand then reacted with p-vinylphenylboric acid. For this cleavage, 13 gof 2,3-O-isopropylidene-D-glyceric acid-(p-vinylanilide) is heated undernitrogen, with stirring, at 80°, with a mixture of 13 g of acid ionexchanger, 300 ml doxane and 300 ml distilled water. The acetone thatforms is removed from the equilibrium by the introduction of a weakcurrent of nitrogen. The reaction was pursued by means of thin-layerchromatography using silica gel, and had ended after 3 hours. Themixture was allowed to cool under N₂, filtered from the ion exchanger,and washed with a small amount of dioxane. The slvent was reduced toabout 80 ml at 30° on the rotary evaporator. The remainder was placed inthe refrigerator until complete crystallization had taken place, andthen was filtered. After drying in the vacuum exsiccator, 10.4 g of rawproduct (95% of the theory) was obtained. After one recrystallizationfrom chloroform, 9.4 g (86% of the theory) of chromatographically puresubstance was isolated. M.P. 137° [α]_(D) ²⁰ = +59.2° (c = 1.26:acetone)

Elemental analysis: C₁₁ H₁₃ NO₃ (207.2): Calculated: C 63.76; H 6.30; N6.76; Found: C 63.30; H 6.15; N 6.95 0.05 -

Alternatively D-glyceric acid -(p-vinylanilide) can be prepared directlyfrom D-glyceric acid and p-aminostyrene on treatment withN,N'-dicyclohexylcarbodiimide as condensing agent: To a solution (cooledto 0° C) of 5.3 g (0.05 mole) D-glyceric acid in 150 ml of acetonitrile,there was added 8.9 g (0.075 mole) β aminostyrene and 10.3 g (0.05 mole)N.N'-dicyclohexylcarbodiimide. A precipitate of N.N'-dicyclohexylurea isformed immediately, but the reaction was allowed to proceed for 15 hoursat room temperature. After filtration and removal of the acetonitrile bydistillation under reduced pressure, the residue was taken up in ethylacetate and extracted with HCl, bicarbonate and water. After drying andremoval of the solvent the residue was crystallized from chloroform,yielding 7.5 g (73%), m.p. 135 - 136° C.

For the preparation of theD-glycericacid-(p-vinylanilide)-2,3-0-(p-vinylphenylboronate), 9.2 g ofD-glycericacid-(p-vinylanilide), 5.8 g of trip(p-vinylphenyl)boroxine(prepared by dehydrating p-vinylphenylboric acid in toluene) and 100 mgof tert.-butylcathechol were boiled under nitrogen in 600 ml ofwater-free benzene in a one-liter flask provided with a water separator.After no more water droplets were separated the solvent was removed onthe rotary evaporator. The residue was extracted three times with 700 mlof boiling petroleum ether (60-95°) each time. The petroleum etherextracts were removed by filtration while hot. Upon cooling, first atroom temperature, then at -20°, the product crystallizes as a voluminousprecipitate.D-glycericacid-(p-vinylanilide)-2,3-O-(p-vinylphenylboronate) is a whitecrystalline powder. Yield: 10 g (71.4% of the theory)

M.p. 143 to 145° C; [α]_(D) = + 176.6 (c = 0.945; water-free dioxane)

Elemental analysis: C₁₉ H₁₈ BNO₃ (319.2): Calculated: C 71.49; H 5.68; B3.39; N 4.39; Found: C 71.55; H 5.64; B 3.47; N 4.48

(2) Preparation of the Polymer

a) General Procedure

The homogeneous polymerization mixture is delivered through a funnelwith a long stem into a thick-walled bomb tube. Then the tube is cooledwith the exclusion of moisture in a mixture of dry ice and methanol andfilled with nitrogen by evacuating it carefully several times andletting raw nitrogen be drawn into it. Then the tube is drawn to athick-walled tip and sealed shut in an oxygen-fed flame, and the seal isthen cautiously and slowly cooled. Then the tube is carefully wrapped ina cloth and placed in an oven (in the metal container in the dryingoven). The oven is heated at 60, 80, 100 and 120° for 24 hours at eachtemperature. Then the tube is chilled in a dry ice and methanol mixtureand the tube is opened by cautiously breaking it. The polymer obtainedis coarsely crushed and dried in vacuo at 40°. Then it is coarselyground and repeatedly washed with ether. Then it is dried again and byfrequent sifting and grinding a maximum percentage is obtained of thegrain size of 63 to 125 microns. The sifted polymer is again washed withether and again dried.

(b) Preparation of Polymerization Mixture I (P-I).

10 g of D-glycericacid-(p-vinylanilide)-2,3-0-(p-vinylphenylboronate),46.5 g (51.3 ml) of a mixture of about 55% divinylbenzene-isomermixture, about 35% ethylvinylbenzene and small amounts ofdiethylbenzene, 60 ml of water-free acetonitrile and 355 mg ofazoisobutyronitrile (AIBN) are polymerized as described above afterbeing divided into 3 ampoules of a capacity of about 100 ml.

6.94 g of polymerization mixture P-I are heated at 70° together with 40ml of 20% HCl in methanol for 16 hours under nitrogen. Then the mixtureis filtered and thoroughly washed with methanol.

In order to free the polymer thus produced (P-Ia) of any HCl that maystill be bound to it, it is stirred with a solution of 1 g of NaHCO₃ in100 ml of a 1:1 mixture of methanol and water for several hours,filtered, and washed thoroughly with MeOH/H₂ O (1:1). To eliminate thelast traces of soluble components, P-Ia is placed in a column and elutedfirst with 400 ml of the MeOH/H₂ O (1:1), then with 400 ml H₂ O andfinally with 200 ml of acetonitrile. Then the polymer is dried in vacuoat about 40°.

This polymer has the following physical data:

Specific surface area: 83 m² /g (by the BET-methode) porosity: main porevolume at 350 degree pore diameter (by Hg-porosimetry)

volume swellability: 5% in acetonitrile (measured in calibrated tubes)

glass transition state: approximately 05° C

(3) Resolution of Racemates

(a) Resolution of DL-glyceric acid: 207.2 mg DL-glyceric acid weredissolved in 45 ml of water-free acetonitrile and stirred for 18 hourswith 4.5 g of Polymer Ia. Then the solution is filtered and the residueis washed four times with 10 ml of water-free acetonitrile each time.

To determine the absorption capacity, the polymer thus obtained(hereinafter referred to as P-Ib) is then dried in the vacuum dryingoven at about 40° and then it is stirred with 10 ml of methanol-watermixture (1:1) for 6 hours in batches of 50 to 100 mg. Then the polymeris filtered out, washed with water, and the methanol is removed invacuo. The aqueous solution is then titrated in the customary manner(of. Table 3).

                  Table 3                                                         ______________________________________                                                         Consumption       Absorption                                                  of 0.025N  Cleavage                                                                             capacity in mg                                              NaIO.sub.4 rate*  glyceric acid                              No.     P-Ib(mg) (ml)       (in %) per g of P-Ia                              ______________________________________                                        1       89.2     1.00       19.2   14.95                                      2       63.6     0.71       19.0   14.90                                      ______________________________________                                         *The cleavage rate relates to the entire equivalent amount of glyceric        acid in P-Ia.                                                            

A total, therefore, of 14.925 × 4.5 = 67 mg of glyceric acid had beenabsorbed by 4.5 g of P-Ia. In the filtrate there still remains 207.2 -67 = 140.2 mg of glyceric acid in the DL and L forms. All of theacetonitrile is distilled out in vacuo to dryness. The residue isdissolved in 10 ml of methanol-water mixture (10:1) and, at roomtemperature, with shaking, a solution of diazomethane in ether is addeduntil a faint yellow color persists. The solvent is removed in vacuo andthe glyceric acid methyl ester enriched with the L form is obtained in avirtually quantitative yield. The optical rotation in 2 ml dioxaneamounts to α_(D) ²⁰ = -0.004 to 0.005°. For further identification theglyceric acid methyl ester is transformed by reaction withtriphenylboroxine in dioxane to the triphenylboroxine derivative whichhas an optical rotation of α_(D) ²⁰ = - 0.033 in 2 ml dioxane. Thisderivative is then reacted in a prior-art manner to formglycericacidmethylester-2,3-0-di(p-nitrobenzoate). This product,purified by means of a chromatography column, has an optical rotation ofα_(D) ²⁰ = + 0.042 (c = 22.1; dioxane).

On the basis of this figure the concentration C₁ of the pure L form maybe computed:

    C.sub.1 = 4.2/34.9 = 0.12 g per 100 ml.

The enrichment of the L form in the filtrate is thus:

    A.sub.l = (C.sub.L /C) · 100 = (0.12/22.1) · 100 = 0.55%.

the enrichment of the D form in the polymer, A_(D), may be calculated inadvance by multiplying A_(L) by a factor F, F being the total amount ofglyceric acid in the filtrate, divided by the total amount of glycericacid on the polymer.

    A.sub.D = A.sub.L · F = 0.55 · (140.2/67) = 1.15%.

the resolving factor α is equal to α_(L) divided by α_(D), α_(L) beingthe total amount of L in the filtrate divided by the total amount of Lon the polymer, and α_(D) being the total amount of D in the filtratedivided by the total amount of D on the polymer:

    α = (50.275/49.425) · (50.575/49.725) = 1.034.

In order to split off the glyceric acid adsorbed by the polymer, P-Ib isplaced in a column and eluted with about 500 ml of methanol-watermixture (1:1). After eliminating the solvent by evaporation, the polymeris transformed, as described above, first to the methyl ester and thento the di-(p-nitrobenzoate) derivative. The optical rotation of themethyl ester was measured in about 1.4 ml of dioxane and amounted toα_(D) (20 = + 0.005°.

From the glycericacidmethylester-2,3,0-di(p-nitrobeazoate) 96 mg wasisolated: α_(D) ²⁰ = - 0.015° (C = 4.8 dioxane)

    C.sub.D = 1.5/34.9 = 0.043 g per 100 ml;

    A.sub.D = 0.043/4.8 · 100 = 0.9% (1.15% had been calculated in advance).

(b) Resolution of DL-glyceric acid methyl ester

(a) 235.9 mg of DL glyceric acid methyl ester was reacted with 4 g ofpolymer P-Ia by the same procedure as with the glyceric acid.

Table 5 shows the cleavage rate of the polymer obtained (P-Id) and theabsorption capacity of P-Ia for glyceric acid methyl ester.

                  Table 5                                                         ______________________________________                                                                         Absorption capac-                                          Consumption of     ity (mg of glyceric                                 P-Id   0.25N NaIO.sub.4                                                                          Cleavage                                                                             acid methyl ester                            No.    (mg)   (ml)        rate (%)                                                                             per g of P-Ia)                               ______________________________________                                        1      188.7  1.01        18.3   16.1                                         2      110.8  0.62        19.0   16.8                                         ______________________________________                                    

In all, therefore, 16.45 · 4 = 65.8 mg of glyceric acid methyl ester wasabsorbed by 4 g of P-Ia. In the filtrate there remains 235.9 - 65.8 =170.1 mg of glyceric acid methyl ester. The filtrate is concentrated byevaporation until dry. The residue is dissolved in about 1.8 ml ofdioxane and the optical rotation is determined: α_(D) ²⁰ = - 0.002°.

Then the phenylborane derivative is prepared from this optically activeglyceric acid methyl ester as described above, and it is dissolved inabout 1.7 ml. of dioxane and its optical rotation is measured: α_(D) ²⁰=- 0.008°.

The 2,3,0-di(p-nitrobenzoate) derivative is then prepared and purifiedin a column. 291 mg of pure product was isolated. α_(D) ²⁰ = + 0.010° (C= 17.1 dioxane);

    C.sub.L = 1/34.9 = 0.0287 g per 100 ml:

    A.sub.L = 0.0287/17.1 · 100  = 0.168% D.sub.D = 0.168 · 170.1/65.8 = 0.44%

    α = 50.084/49.78 · 50.22/49.916 = 1.012

(β) 8.7 g of a once used and again regenerated polymer Ia was reacted asdescribed above with 315 mg of DL-glyceric acid methyl ester inwater-free dioxane as solvent.

The cleavage rate of the polymer obtained, as well as the absorptioncapacity of P-Ia, are identical to the corresponding values inExperiment (α).

The ester in the filtrate was transformed to the phenylboranatederivative, and dissolved in 1.7 ml of dioxane; the optical rotation wasthen determined : α_(D) ²⁰ = - 0.006° ; A_(D) = 0.15% (estimated).

(γ) 10 g of P-Ia was stirred for several days with dioxane at roomtemperature, then heated for 6 hours at 80°. The polymer was then driedin vacuo at 40° and reacted in the usual manner with 813 mg ofDL-glyceric acid methyl ester. Despite this pre-treatment of thepolymer, the absorption capacity was no different than in Experiments(α) or (β); enrichment in the optical antipodes was not found on thebasis of this pre-treatment.

(c) Resolution of DL-glycerinaldehyde.

198 mg of DL-glycerinaldehyde is dissolved in 15 ml of water and letstand for 20 hours. Acetonitrile is dripped in under nitrogen and at thesame time the acetonitrile-water is removed by azeotropic distillationuntil the vapor temperature reaches 81.5°. Then 50 ml of water-freeacetonitrile is added and the distillation of about 20 ml of solventcontinues. After cooling, the mixture is reacted with 4 grams of P-Ia asusual.

Table 6 shows the cleavage rate of the polymer obtained (P-Ia) and theabsorption capacity of P-Ia for glycerinaldehyde.

                  Table 6                                                         ______________________________________                                            P-Ia                 Cleavage                                                                             Absorption cap. in                                in       Consumption of                                                                            Rate   mg glycerinaldehyde                           No. mg       NaIO.sub.4 in ml                                                                          %      per g of P-Ia                                 ______________________________________                                        1      73.4  0.76        17.7   11.7                                          2     109.7  1.16        18.2   11.9                                          ______________________________________                                    

Therefore a total of 11.8 · 4 = 47.2 mg of glycerinaldehyde has beenabsorbed by 4 g of P-Ia. 198 - 47.2 = 150.8 mg of glycerinaldehyderemains in the filtrate.

The filtrate is concentrated by evaporation until dry. The concentrateis dissolved in about 1.5 ml of water and reacted with 400 mg ofdimedone to form glycerinaldehydedimedone. The raw product is purifiedthrough a silica gel column, 42 mg of chromatographically pure productbeing isolated.

    α.sub.D.sup.20 = -0.018° (c = 2.1; ethanol)

    C.sub.L = 1.8/197.5 = 0.0091 grams per 100 ml;

    A.sub.L = 0.0091/2,1 · 100 ' 0.43%;

    A.sub.D = 0.43 · 150.8/47.2 = 1.37%

    α= 50.215/49.315 · 50.685/49.785 = 1.036

EXAMPLE 2 (a) Preparation of D-mannitol-tri-(p-vinylphenylboronate9 asthe monomer to be polymerized.

7.25 g of p-vinylphenylboric acid (or 6.4 g of p-vinylphenyloboric acidanhydride) was dissovled in 7.5 ml of methylanol at 50° C. Also, 2.72 gof D-mannitol was dissolved in 4.5 ml of water at 50° C. The mannitolsolution was added to the boric acid solution, whereupon a white pasteprecipitated. This was filtered, washed with methanol-water mixture(2:1) and dissolved in 100 ml of benzene for recrystallization. Afterthe removal of the remaining turbidity the filtrate was concentrated to50 ml and then 65 ml of petroleum ether was added. The esterprecipitated again. This recrystallization was repeated twice; the yieldof pure product thus obtained amounted to 5.8 g =75%.

MP = 158 - 160° C [α]₁₀ ⁴³⁶ +144.0°

Elemental analysis: Found C69.50%; H 5.60%; B 6.28% Calculated: C69.42%; H 5.70%; B 6.15%

(b) Preparation of the polymer.

Two grams of D-mannitol-tri-(p-vinylphenylboronate) together with 2 mlof methacrylic acid methyl ester, 4 ml of ethylene glycol dimethacrylicacid ester and 100 mg of α,α'-azo-diisobutyronitrile are dissolved in 4ml of benzene and placed in a bomb tube. Washing is performedportion-wise with another 4 ml of benzene. Then the mixture is washedthree times with nitrogen at -70° C and then, after the bomb tube hasbeen sealed, it is heated at temperature between 60 and 120° C. Thepolymer obtained (P-III) is crushed, freed of solvent in vacuo at 40°,and then ground. The specific surface area was found by the BET methodto be 180 m² /g.

In like manner a polymer P-IV) was prepared, in which acetonitrile wasused as solvent instead of benzene.

In addition, a polymer P-V was prepared in a manner similar to P-I, 2 ml=2.19 g of indene being used instead of the methacrylic acid ester.

(c) Splitting off the matrix.

2.0 g of a polymer prepared as in (b) was rinsed for 12 hours with amixture of methanol and water (1:3). After this operation, 79,8% of theD-mannitol contained in the polymer had been split off. Continuing thistreatment for an additional 24 hours resulted in a cleavage rate of86.1%. Then the polymer was rinsed for 36 hours with about 750 ml of amixture of ethanol and water (8:2) to which 3% glycol had been added,and then it was again washed out with methanol.

(d) Determining the resolving factor.

The resolving factors of polymers freed of the matrix in this mannerwere determined with respect to DL-mannitol. The following generalprocedure was used: DL mannitol was brought in contact with the polymer,free of the matrix, in a suspension. After the esterificationequilibrium had established itself, filtration was performed, and theamount of the mannitol in the filtrate was determined by the filtrationof an aliquot part. The rest was used for determining the opticalactivity. Titration is used to determine the amount of mannitol in thefiltrate c_(F) and the rotation was used to determine also thequantities of the D and L components c_(FD) and c_(FL) Furthermore, .the portion of the racemate that remained in the polymer was split offfrom the polymer and c_(p), c_(PD) and C_(PL) were determined in thesame manner.

On the basis of these measurements the resolution factor α wasdetermined for the above-named polymers. The resolution factors givenhereinbelow apply on the condition that, in each case, 46 mg of theracemate is brought into contact for a time of 6 hours with the polymerobtained in accordance with (c), at a temperature of 50° C. Under theseconditions the resolution factor for polymer III was 1.065, for polymerIV it was 1.083 and for polymer V it was 1.090.

EXAMPLE 3

(1) Preparation of D-mannitol - 1,2; 3,4; 5,6 - tri - 0 -(p-vinylphenylboronate) as the monomer to be polymerized.

Preparation of the Monomer

This monomer is prepared in one step from D-mannitol andp-vinyl-phenyl-boronic acid. 1.82 g D-mannitol are dissolved in 3 mlwater at 50° C and 4.83 p-vinyl-phenyl-boronic acid, dissolved in 5 mlmethanol at 50° C are added. The product crystallizes immediately aswhite thick crystals. It is filtered, washed twice with methanol/water2:1 and dried in a desiccator. The product is dissolved in 50 mlbenzene, filtered, evaporated to 25 ml and 25 ml of petrol ether isadded. Large white crystals are obtained. M.P. 166° C; [α]₄₃₆ ²⁰ + 144°(c=1.0, chloroform); Yield 3.9 g (63% of the theory)

Elemental analysis: C₃₀ H₂₉ O₆ B₃ (518.0): calc: C 69.50; H 5.60; B6.28; found: C 69.32; H 5.46; B 6.68.

Preparation of the Polymer

2 g D-mannitol - 1,2; 3,4; 5,6 -tri - 0 -(p-vinylphenylboronate), 12 mlacetonitrile, 4 ml methylmethacrylate 5.3 ml glycoldimethacrylate, and75 mg azoisobutyronitrile (A I B N) are polymerized as described inexample 1. The D-mannitol of the produced polymer is dissolved bytreating the polymer in a column at 50° with a mixture of methanol/water1:1. After eluting with 2 l of solvent during 24 hours more than 80percent of D-mannitol are removed from the polymer. The polymer shows agood resolving power for the racemate D,L-mannitol. Furthermore oneobtains good chromatographic separations between mannitol, sorbitol anddulcitol.

EXAMPLE 4

Preparation of N-(p-vinyl-benzylidene) L-phenylalanine-(p-vinyl-anilide) as the monomer to be polymerized.

Preparation of the Monomer

N-Trifluoroacetyl-L-phenylalanine is dissolved in tetrahydrofuran andtreated with p-vinyl-anilinein presence of N,N'dicyclohexylcarbodiimide. N-Trifluoracetyl - L - phenylalanine(p-vinylanilide) isformed in high yield and without racemization. Thetrifluoracetyl-residue is removed by hydrolysis with diluted mineralacid at room temperature. L - Phenylalanine (p-vinylanilide) is thentreated with p-vinyl-benzaldehyde in methanol at 50° and the Schiffbaseis formed in high yields.N-(p-vinylbenzylidene)L-phenylalanine(p-vinyl-anilide) is a crystallinerather stable compound, but should be stored at -20° and somepolymerization inhibitor should be added in order to suppresspolymerisation.

Preparation of the Polymer

5 g N-(p-vinyl-benzylidene L-phenylalanine-(p-vinyl-anilide) 8 mlbenzene, 8 ml acetonitrile, 6 ml pure p-divinylbenzene, 5 ml indene, and200 mg azoisobutyronitrile (A I B N) are polymerized in a sealed tube atroom temperature by irridation with U V -light of 254 mμ.

L-Phenylalanine is split off from the produced polymer by heating it at70° C together with 20% HCl in methanol for 20 hours under nitrogen.Then the mixture is filtered and thoroughly washed with methanol, with asolution of 1 g NaHCO₃ in methanol/water 1:1 and with methanol/water1:1. This polymer when treated with D,L-phenylalanine absorbspreferentially L-phenylalanine, thus giving the possibility forresolution of the racemate.

EXAMPLE 5

Preparation of D-tartaric acid - mono - n - octylester - 2,3-0-(p-vinyl-phenylboronate)-(p-vinyl-anilide) as the monomer to bepolymerized.

Preparation of the Monomer

The tartaric acid - mono - n - octylester is dissolved intetrahydrofuran and treated with p-vinyl-anilinein presence ofN,N'-dicyclohexyl-carbodiimide, D-Tartaric acid - mono - n - octylester(p-vinyl-anilide) is formed in high yields. This product is boiled withtri- (p-vinyl-phenyl)boroxine in benzene in a flask provided with awater separator. In nearly quantitative yield D-tartaric acid - mono -n - octylester - 2,3 -0- (p-vinyl-phenyl-boranate)- (p-vinylanilide) isformed.

Preparation of the Polymer

5 g D-tartaric acid - mono - n - octylester - 2,3 - 0-(p-vinylphenylboronate) - (p-vinyl-anilide), 8 ml cyclohexane, 8 mlethylacetate, 5 ml dodecene - 1, 6ml pure p-divinylbenzene and 200 mgdibenzoylperoxide are polymerized in a sealed tube at temperaturesstarting at 50°, to 60°, 70° and 80° during 3 days. D-tartaric acidn-octylester is split off by treating the polymer with 25 percentammonia in methanol at room temperature for a period of 20 hours. Thepolymer is washed thoroughly with methanol and methanol/water 1:1. Thepolymer shows good resolution power for D,L-tartaric acidmono - n -octylester.

EXAMPLE 6

Preparation of isophthalic acid - m - sulfon -(N-D-1-phenylethyl)amideas a monomer to be polycondensated.

Preparation of the Monomer

Isophthalic acid - di - benzylester is sulfonated in tetrachloromethaneby introducing gaseous SO₃, the reaction is at first cooled by ice,later on it is heated under evaporation of the solvent to 110° C for 2hours. Isophthalic acid - di - benzylester - m - sulfonic acid istreated with SO₂ Cl₂ to transform the compound to the sulfonic acidchloride, which then is treated without further purification with D -α - phenylethylamine in pyridine as solvent. The isophthalic - acid -di - benzylester - m-sulfone- (D-α-phenylethylamide) is obtained in goodyield. The benzylester groups are split off by catalytic hydrogenationin diethylether in presence of Pt.

Preparation of the Polymer.

Isophthalic acid - m - sulfone (D-α-phenylethylamide) in mixture withtrimellitic acid is treated with SO₂ Cl₂ in presence of some pyridineand thus converted to the acid chlorides. These are dissolved inmethylene chloride and under vigorous stirring poured to a solution ofethylendiamine and potassium hydroxide in water. After 20 minutes atroom temperature the white amorphous polymer is filtered, thoroughlywashed and dried. The D - α - phenylethylamine residues are split off bytreating the polymer with 2% HCl in methanol at 50° for 20 hours. Theproduced polymer shows a good resolving power for D,L - α -phenylethylamine and similar racemic amines.

EXAMPLE 7

Preparation of oestradiol - 3 - o - (2,4 -dicyanato-toluene-6-sulfonate) as a monomer for a polyaddition polymer.

Preparation of the Monomer.

2.4 - Dinitrotoluene is sulfonated with oleum/sulfonic acid, and 2.4 -dinitro-toluene - 6 - sulfonic acid is obtained. The sulfonic acid istransformed to the acid chloride with SO₂ Cl₂ in presence of somepyridine. The SO₂ Cl₂ is evaporated and the residue is dissolved inpyridine. Oestron is added and the solution is worked up after 24 hoursstanding. It is poured into ice water and after 3 hours filtered andwashed thoroughly with water. The residue is purified bycrystallization. Oestron - 3 - o - (2.4 - dinitro-toluene-6-sulfonate)is hydrogenated in methanol in presence of Pd on charcoal to yieldoestradiol - 3 - o - (2.4-diamino-toluene-6-sulfonate). This diaminocompound is treated in tetrahydrofuran at 0° C with phosgene, afterwardsthis treatment is continued at 60 - 70° C. After evaporation of thesolvent the residue of oestradiol - 3 - o -(2.4-dicyanato-toluene-6-sulfonate) is purified by crystallization.

Preparation of the Polymer.

Oestradiol - 3 - o - (2.4-dicyanato-toluene-6-sulfonate) is reacted witha mixture of 1.4 - butandiol and glycerine in tetrahydrofuran inpresence of triethylendiamine at 50° C for 5 hours. The insolublepolymer is thoroughly washed with methanol and then treated with 1 percent HCl in methanol at 50° C for a period of 10 hours. By thisprocedure most of the oestradiol is split off and in the polymer arecavities left with sulfonic acid residues. This polymer can be used forthe resolution of racemic mixtures of oestron as well as of oestradiol,obtained by total synthesis of these substances.

EXAMPLE 8

Preparation of mandelic acid (p-hydroxy anilide)- (o-hydroxybenzoate) asa monomer to be polycondensated.

Preparation of the Monomer

Mandelic acid is treated with p- hydroxy - aniline andN,N'-dicycloexylcarbodiimide in tetrahydrofuran at room temperature for10 hours. The obtained mandelic acid - (p-hydroxy-anilide) is thendissolved in tetrahydrofuran/pyridine 5:1 and treated with salicyclicacid and N,N' - dicyclohexyl-carbodiimide, whereupon in good yields theester is formed. Mandelic acid -(p-hydroxy-anilide -(o-hydroxy-benzoate) is a stable crystalline compound.

Preparation of the Polymer

Mandelic acid - (p-hydroxy-anilide)- (o-hydroxy-benzoate), phenol andformaldehyde in water are heated with a small amount of oxalic acid for2 hours at 100° C. After addition of water the resin is separated. Aftercooling it is crushed and thoroughly mixed with celite, hexamethylenetetramine and magnesium oxide. This product is tempered at 160° C for 10minutes.

The produced polymer is treated with 20 per cent HCl in methanol for 20hours under nitrogen at 80° C. Under these conditions the mandelic acidis split off to a high percentage. This polymer can be used for theresolution of D,L-mandelic acid.

Additional Examples of the Introduction of Functional Groups intoPolymers in an Arrangement Analogous to Enzymes (A) With only onefunctional group:

The following two examples (as well as Examples 6 and 7 supra) clearlyshow that racemate resolution is possible even where only one functionalgroup is introduced. Such resolution is accomplished due to the positionof the group in the microcavity and to the shape of the microcavity.

EXAMPLE 9

Preparation of D-1,2- propanediol-(p-vinylphenylboronate) as monomer forthe polymerization.

Preparation of the Monomer

1.52 g (0.02 mole) of D-1,1-propanediol was heated to ebullition with2.96 g (0.02 mole) of p-vinylphenylboric acid in methylene chloride andthe water that formed was separated in the water separator. After 2hours the reaction had ended, the solvent was removed by distillationand the residue was dissolved in petroleum ether. After filtering outthe unreacted p-vinylphenylboric acid, the reaction mixture wasconcentrated again and distilled in vacuo. Yield 2.6 g (70%), BP 57° Cat 0.3 mm. [α]_(D) ²⁰ = + 16.9° (c = 0.26, dioxane). C₉ H₁₃ BO₂ : Calc.:C 70.29; H 6.93; B 5.75; Found: C 70.27; H 7.00; B 5.71

Preparation of the Polymer

In two batches, 1.54 g (0.008 mole) ofD-1,2-propanediol-(p-vinylphenylboronate), 8.19 g (approx. 0.063 mole)of tech. divinylbenzene mixture (55% divinylbenzene) and 100 mg ofazoisobutyronitrile were polymerized in 8.9 ml of solvent. The solventfor batch P I was acetonitrile, and for batch P II it was benzene. Thepolymerization was performed thermally at temperatures increasing from60° to 120° C. After crushing to 63-125 μ grain diameter, theD-propanediol matrix was split off with a 1:1 mixture of methanol andwater by the flow-through method. The cleavage rate amounted toapproximately 80-90% for both polymers.

For the determination of the racemate resolving ability, 4.5 g of thepolymer prepared was stirred in each case with 500 mg ofD,L-1,2-propanediol. Then the mixture was filtered and the absorbed1,2-propanediol was split off from the polymer again by elution with a 1: 1 mixture of methanol and water. The filtrate and the elution solutionwere concentrated separately and the 1,2-propanediol obtained wastransformed in each case to the 1,2-propanediol-di-O-(p-nitrobenzoate)whose rotation was then determined. The racemate resolving ability wasjudged on the basis of the rotation. The resolution factors α were 1.015for P I and 1.013 for P II.

EXAMPLE 10

Preparation of D-glyceric acid methyl ester2,3-O-(p-vinylphenylboronate)as monomer for polymerization.

Preparation of the Monomer

7 g (0.058 mole) of D-glyceric acid methyl ester was transformed with8.6 g (0.058 mole) of p-vinylphenylboric acid to the phenylboronate inthe same manner as in the foregoing example.

Purification by distillation at 5 × 10⁻⁵ Torr. B.P. 109°-112° C. Yield8.4 g (63%), [α]_(D) ²⁰ : +58.7° (c = 1.1, dioxane).

NMR (CDCl₃): δ 3.70 (s, 3 H of COOCH₃), 3 glyceric acid protons, ABMspectrum (δ_(A) 4.25, δ_(B) 4.48, I_(AB) = 8.5 Hz, I_(AM-BM) = 7.5 Hz,δ_(M) = 4.92 (t): 3 H of the vinyl group, AMX spectrum (δ_(A) 5.22,I_(AM) = 1.5 Hz, I_(AX) = 10.5 Hz, δ_(M) 5.70, I_(MX) = 17.5 Hz, δ_(X) =6.65 q) 4 H of the aromatic, A² B² spectrum (δ_(A) 7.72, δ_(B) 7.31,I_(AB) = 8.0 Hz).

C₁₂ H₁₃ BO₄ (232.1): Calc.: C 62.11; H 5.65; B 4.66; Found: C 61.93; H5.78; B4.56

Preparation of the Polymer

1.5 g of D-glyceric acid methyl ester -2,3-O-(p-vinylphenylboronate),9.7 g of tech. divinylbenzene (55% pure), 100 mg of azoisobutyronitrileand 11.2 ml of acetonitrile were polymerized in the usual manner. Thematrix was split off again (to about 50%) with a 1:1 mixture of methanoland water. The polymer thus prepared had a resolving factor forD,L-glyceric acid methyl ester of α = 1.030.

B. With Additional Interactions of Polymer Matrix and Matrix

If comonomers are added in the polymerization which are capable ofinteracting with certain structural parts of the matrix, they arrangethemselves in the microcavity during the polymerization such that, afterthe matrix is cleaved off, they substantially facilitate the specificreattachment of the matrix. Thus the function as an additional adhesiongroup and considerably increase the specificity of the racemateresolution.

EXAMPLE 11 INTERACTION OF ESTER AND BORIC ESTER GROUP WITH VINYLPYRIDINE PREPARATION OF THE POLYMER

1.5 g of D-glyceric acid methyl ester-2,3-O-(p-vinylphenylboranate), 5.4g of glycol dimethacrylate, 4.3 g of m-vinylpyridine, 100 mg ofazoisobutyronitrile and 11.2 ml of acetonitrile were polymerized in theusual manner.

The cleavage rate with a 1:1 mixture of methanol and water was 36.7%.The specificity of the racemate resolution for D,L-glyceric acid methylester was higher than in Example A2.

EXAMPLE 12

Hydrophobic interaction between two octyl-alcohol moieties in thepolymerization of D-glycericacid-n-octylester-2-3,-O-(p-vinylphenylboronate).

Preparation of the Monomer

10 g (0.095 mole) of D-glyceric acid was heated with 900 ml of n-octanoland 0.5 g of p-toluenesulfonic acid for 1 hour on the water separator,with refluxing. Then the mixture was cooled and 0.5 g of dry potassiumacetate was added to inactivate the p-toluenesulfonic acid, and theexcess n-octanol was removed by distillation in a water jet vacuum. Theresidue was distilled at 0.01 Torr and 13 g (62%) was obtained having aBP₀.01 of 102°-104° C. It was difficult to free this product ofn-octanol residues by distillation, so this was accomplished bychromatography on SiO₂ with a mixture of benzene, acetone and petroleumether (60/90) in a ratio of 12:8:3 as the vehicle. The product wasD-glyceric acid-n-octylester: [α]_(D) ²⁰ : + 18.8° (c = 1.1, dioxane)[Literature: BP₁₃ 181°-183°, [α]_(D) ¹⁹ : +10.2° ]. The ester preparedin the bomb tube at 145°-155° according to the literature must havecontained considerable amounts of n-octanol.

C₁₁ H₂₂ O₄ (218.3): Calculated: C 60.52; H 10.16; Found: C 60.44; H10.15

D-glyceric acid-n-octylester-2,3,-O-(p-vinylphenylborenate) was thenobtained by the reaction of D-glyceric acid-n-octylester withp-vinylphenylboric acid. Yield 65%, BP 130° C at 10⁻⁴ Torr. [α]_(D) ²⁰ :43.2° (c= 1.0, (dioxane).

C₁₉ H₂₇ BO₄ (330.2): Calc.: C 69.11; H 8.24; B 3.27; O 19.38; Found: C68.86; H 8.37; B 3.31; O 19.36

EXAMPLE 12 (Continued) Preparation of the Polymer

1.5 g of D-glyceric acid-n-octylester-2,3,-O-(p-vinylphenylboronate),3.85 g of glycoldimethacrylate, 2.95 g of n-octylmethacrylate, 100 mg ofazoisobutyronitrile and 8.3 ml of acetonitrile were polymerized asdescribed before. The splitting off of the matrix was performed with 90%ethanol. The specificity for the resolution of the racemic D,L-glycericacid-n-octylester is markedly greater than in Example 10.

EXAMPLE 14.

interaction between aromatics in the polymerization ofD-glycericacidbenzylester-2,3,-0-)p-vinyl-phenylboronate).

Preparation of the Monomer

32.4 g (0.27 mole) of D-glyceric acid methyl ester was heated with 150ml of acetone and 0.8 g of p-toluene-sulfonic acid in 1300 ml ofmethylene chloride with refluxing through a column with a waterseparator until no more water was formed (approx. 14 hours). Then themixture was cooled to 0° C and washed with a KOH solution (2 g KOH in120 ml of water) of 0° C, then washed twice with 100 ml each time ofwater of 0 ° C, dried with potassium carbonate, and then, after drawingoff the solvent, it was distilled in the water jet vacuum. BP₁₂ mm 77°,yield of 2,3-Q-Isopropylidene-D-glycericacidmethylester 38.0 g (88%) ofa colorless, very fluid liquid. [α]D₂₀ : +8.1° (c = 1.5, acetone). NMR(CDCl₃): δ 1.40 and 1.49 (2s, 6 H of the isopropylidene group), 3.75 (s,3 H of the methyl ester protons), the three glyceric acid protons forman ABM system δ_(A) = 4.20, δ_(B) = 4.00, I_(AB) = 8.5 Hz, I_(Am=BM) = 6Hz, δ_(M) = 4.57 (t).

C₇ H₁₂ O₄ (160.2): calculated: C52.49; H 7.55;

Found: C52.31; H 7.41

14.4 g (0.09 mole) of 2,3-O-isopropulidene-D-glyceric-acidmethylesterand 14 g (0.077 mole) of benzyl alcohol (freshly distilled) were heatedwith 0.4 g (0.002 mole) of aluminum isopripylate, with stirring, invacuo (12 Torr), for 9 h at 70° C and 4 h at 90° C, while a carbondioxide-free stream of air was drawn through the solution through acapillary. Then the reaction mixture was distilled in vacuo, producing16.1 g of 2,3-O-isopropylidene-D-glycericacidbenzyl-ester, BP₀.01 mm100-103°. Residues of benzyl alcohol were removed by chromatography onsilica gel with a vehicle of benzene, acetone and petroleum ether mixedin a ratio of 12:8:3. [α]_(D) ²⁰ : +14.1° (c = 1.2, dioxane). NMR(CDCl₃): δ1.34 and 1.46 (2 s, 6 H of the isopropylidene group), 3glyceric acid protons, ABM spectrum: δ_(A) 3.98, δ_(B) 4.16, I_(AB) = 9Hz, I_(AM=BM) = 6 Hz, δ_(M) 4.51 (t); 5.07 (s, benzyl-CH₂), 7.20 (s, 5aromatic protons).

C₁₃ H₁₆ O₄ (236.3): Calculated: C 66.09; H 6.83; Found: C 66.16; H 6.66

16 g (0.068 mole) of 2,3-O-isopropylidene-D-glyceric-acidbenzylester washydrolyzed at 50═ with 15 g of Amberlyst 15 in 350 ml of dioxane with 1%water for 8 hours. To emove small amounts of free gylceric acid, themixture was filtered through silica gel with a solvent composed ofbenzene, acetone and petroleum ether, 12:8:3. Yield ofD-glycericacidbenzylester 9.5 g (70%) of an oil which solidified at -10°C. [α]_(D) ²⁰ : + 18.0° (c = 1.2, dioxane).

C₁₀ H₁₂ O₄ (196.2) Calculated: C 61.22; H 6.16; Found: C 60.73; H 6.01

Preparation of the p-vinylphenylboronate was analogous to the previousexamples. Refinement performed by crystallization from petroleum ether60/90. Yield of D-glycericacidbenzylester-2,3-Q-(p-vinylphenylboronate):80%, in colorless flakes with a 40° C melting point, [α]_(D) ²⁰ : +55.7°(c = 1.2, dioxane).

C₁₈ H₁₇ BO₄ (308.2): Calculated: C 70.16; H 5.56; B 3.51; Found: C69.92; H.5.51; B 3.25

Prepartion of the Polymer

1.5 g of D-glycericacid benzylester- 2,3-O-(p-vinylphenylboronate), 7.2g of tech. divinylbenzene (55% pure), 100 mg of azoisobutyrontrile and9.5 ml of acetonitrile were polymerized in the usual manner. Thesplitting off of the matrix was perfomed with 90% ethanol.

The polymer had a good capacity for the resolution of D,L-gylceric acidbenzyl ester.

EXAMPLE 15.

Electron Donor-Accepter Complexes (charge transfer complexes) in thePolymerization ofD-gylcericacid-p-nitrobenzylester-2,3-O-(p-vinylphenylboronate).

Preparation of the Monomer

10 g (0.065 mole) of p-nitrobenzyl alcohol and 7 g (0.044 mole) of2,3-O-isopropylidene-D-gylcericacidmethylester were first homogenized byheating at 100°. After the addition of 0.4 g (0.002 mole0 of aluminumisopropylate the mixture was heated in vacuo for 1 hour at 110° asdescribed in the case of the benzyl ester. The reaction product wascrystallized from a mixture of methanol and water, yielding 9.2 g (55%)of 2,3-O-isopropylidene-D-gyleric acid-p-nitrobenzyl-ester in long,yellow needles having a melting point of 62.5°, [α]_(D) ²⁰ : +8.5° (c =0.8, dioxane).

C₁₃ H₁₅ NO₆ (281.3): Calculated: C 55.52; H 5.37; N 4.98; Found: C55.67; H 5.32; N 5.28

By hydrolysis of the isopropylidene derivative rhombic crystals wereobtained in an 84% yield [from a 12:8:3 mixture of benzene, acetone andpetroleum ether], of D-glyceric acid-p-nirtobenzylester of MP 57°,[α]_(D) ²⁰ : + 29.2° (c = 1.0, dioxane). The NMR (DMSO) showed theexpected proton ratios.

C₁₀ H₁₁ NO₆ (241.2): Calculated: C 49.80; H 4.59; N 5.81; Found: C49.59; H 4.94; N 5.50

The p-vinylphenylboronate ws prepared as decribed above. Crystallizationfrom benzene/petroleum ether 60/90° resulted in an 86% yield ofD-glycericacid-p-nitrobenzylester-2,3-O-(p-vinylphenylboronate) in theform of colorless needles of MP 99-103° C, [α]_(D) ²⁰ : + 46.5° (c =1.1, dioxane). NMR (CDCl₃): 6 H of the p-nitrobenzyl radical (δ 5.24,(s, -CH₂); H of the aromatic in the form of an AB spectrum, δ_(A) 7.41,δ_(B) 8.06, I_(AB) = 8.5 Hz).

C₁₈ H₁₆ BNO₃ (353.2): Calc.: C 61.22; H 4.57; B 3.06; N 3.97; Found: C60.84; H 4.53; B 3.51; N 4.00

Preparation of the Polymer

1.5 g pof the monomer, 4.0 g of glycol dimethacrylate, 2.35 g ofp-dimethylaminostyrne, 100 ml of azoisobutyronitrile and 7.9 ml ofacetontrile were polymerized in the usual manner. As soon as the mixingand polymerization took place there appeared the intense yellow-redcoloration of a charge transfer compex, which has not appeared in theprevious polymerizations.

The polymer thus prepared has a very good capacity for the resolution ofD,L-glycericacid-p-nitrobenzylester.

EXAMPLE 16

Electrostatic Interactions in the Polymerization ofD-glycericacid-p-hydroxybenzylester-2,3-O-(p-vinylphenylnoronate).

Preparation of the Polymer

1.5 g of the monomer prepared as specified above from p-hydroxybenzylalcohol was polymerized with 3.85 g of glycoldimethacrylate, 2.95 g ofp-(dimethylaminomethyl)styrene, 100 mg of azoisobutyronitrile and 8.3 mlof acetonitrile. The splitting off of the matrix ws performed withmethanol mixed with 0.1N aqueous HCl 1:1. The specificity for theresolution of D,L-glyceric acid-p-hydroxybenzylester is considerablyhigher than in Example 10 and 14.

EXAMPLE 17

Additional Electrostatic Interactions Between Tertiary Amine andCarboxyl Group in the Polymerization ofEcgonine-3-benzoate-[(p-vinylphenyl)-methyl]-amide

Preparation of the Monomer

2.89 g (0.01 mole) of ecgonine monobenzoate (desoxymethylcocaine) wasreacted in the presence of 2.47 g (0.012 mole) ofN,N'-dicyclohexylcarnodiimide with 2.4 g (0.02 mole) ofp-aminomethylstyrene in 200 ml of tetrahydrofuran. After 8 hours ofstanding at room temperature, the precipitated urea was removed byfiltration and the solution was concentrated. After repeatedrecrystallization, ecgonine-3-benzoate-[(p-vinylphenyl)-methyl]-amide isobtained in pure form.

Preparation of the Polymer

2 g of the monomer, 0.7 g of methacrylic acid, 7.0 g of technicaldivinylbenzene (55% pure) and 100 mg of azoisobutyronitrile werepolymerized in 9 ml of acetonitrile in the usual manner. The matrix waslargely split off by heating in an ampoule at 80° with 20% HCl inmethanol.

The polymer contained free amino groups and carboxylic groups and wasvery well suited for the resolution of the racemic mixture ofecgonine-3-benzoate and 1,2,3,5-isoecgonine-3-benzoate.

Examples of the Introduction of Functional Groups of Modified ReactivityHaving the Same Matrix.

In order to introduce into the polymer functional groups of preciselygradated reactivity and mobility, the monomer can either be modified inits structure (see Examples 18-23) or its properties can be modified bychemical reaction in the finished polymer after splitting off the matrix(see Examples 24-25).

EXAMPLE 18

Introduction of an amino group of greater conformative mobility andbasicity by the polymerization ofD-glycericacid-[2(p-vinylphenyl)]-ethylamide-2,3-O-(p-vinylphenyl)-boronate.

Preparation of the Monomer

Analogously to the previously described preparation ofD-glycericacid-p-vinylanilide, 16 g (0.11 mole) ofp-(2-aminoethyl)-styrene was reacted by the Boudrousx method with 8.8 g(0.055 mole) of 2,3-O-isopropylidene-D-glyceric acid-methyester to formthe amide. The liquid raw product (14 g) was hydrolyzed directly in 660ml of a 2:1 mixture of dioxane and water with 14 g of Amberlyst 15.

5 g (39%) of D-glycericacid-[2(p-vinylphenyl)-ethylamide was obtained inthe form of chromatographically uniform, colorless crystals(recrystallization from chloroform) with a melting point of 129°,[α]_(D) ²⁰ : +21.2° (c = 1.0, acetone). NMR (acetone-d₆ = D₂ O): δ 2.78(t, I = 7 Hz, 2 H of the α-CH₂), 2.92 (s, 2 H of OH), 3.20-4.20 (m, 5 Hof the glyceric acid and the β-CH₂), 3 H of the vinyl group, AMX systemδ_(A) 5.10 (q, I_(AM) = 1.5 Hz, I_(AX).sbsb.2 = 10.5 Hz, δ_(M) 5.64 (q,I_(MX) = 17.5 Hz) δ_(X) 6.66 (q), 4 H of the aromatic, A² B² system(δ_(A) 7.12, δ_(B) 7.28, I_(AB) = 8.5 Hz) δ 7.38 (s, 1 H of the amideproton).

C₁₃ H₁₇ NO₃ (235.3): Calc.: C 66.36; H 7.28; N 5.95; Found: C 66.20; H7.37; N 5.80

D-glycericacid-[2-(p-vinylphenyl)]-ethylamide-2,3-O-(p-vinylphenyl)-boronatewas obtained by reaction with tri-(p-vinylphenyl)-boroxine in a yield of73%, colorless crystals (from petroleum ether 60/90) of MP 138-139° C[α]_(D) ²⁰ : +66.1° (c = 1.0, acetone).

C₂₁ H₂₂ BNO₃ (347.2): Calc.: C 72.64; H 6.38; B 3.12; N 4.03; Found: C72.23; H 6.50; B 3.44; N 4.09

Preparation of the Polymer

1.5 g of the above described monomer was polymerized with 7.2 g oftechnical divinylbenzene (55% pure), and 100 mg of azoisobutyronitrilein 9.5 ml of acetonitrile. After crushing, and cleaving off the matrixwith 20% methanolic HCl at 100° in the bomb tube, a polymer was obtainedcontaining phenylboric acid groups and β-phenylethylamine groups. Thepolymer had a good capacity for the resolution of D,L-glyceric acid.

EXAMPLE 19.

Introduction of a β-Phenylethylboric Acid Group and an Aniline Group byPolymerization ofD-glycericacid-(p-vinylanilide)-2,3-O-[2-(p-vinylphenyl)]-ethylboronate.

Preparation of the Monomer

To prepare 2-(p-vinylphenyl)-ethylboric acid, 4,5 g (0.187 mole) ofmagnesium chips were activated with 5 ml of ethylbromide in 10 ml of dryTHF at room temperature and under N₂ for a short time. The supernatantsolution was removed, 20 ml of THF was added, and 24 g (0.118 mole) ofp-(β-bromoethyl)-styrene in 100 ml of THF was added drop by drop suchthat the solvent was barely boiling (approx. 20 minutes). Thereafter themixture was allowed to continue to react and then it was chilled to -78°C. This Grignard solution was added in portions to a solution, alsochilled to -78°, of 27 g (0.117 mole) of tri-n-butylborate in 60 ml ofdry ether. The mixture was allowed to warm up to room temperatureovernight, with stirring, and was poured into an ammonium chloridesolution (250 g NH₄ Cl in 750 ml of water) of 0° C temperature. Theorganic phase was separated and the aqueous removed by shaking threetimes with 100 ml of ether. After the addition of 0.1 g of tert.butylcatechol, the organic phase was concentrated; 100 ml of water wasadded and the mixture was concentrated by evaporation in vacuo at 30°,this operation being performed four times to remove the n-butanolazeotropically. The residue was treated four times with water at 80°,the main part of the insoluble polymer was removed by filtration, andcrystallization was produced at 0° C. Yield: 2.5 g (12.5%) colorlesscrystals, MP 75° C. If dried under CaCl₂ in the vacuum exsiccator toform the boroxine, polymerization took place. Consequently the productwas suction dried in an air stream. NMR (methanol-d₄): In addition tothe protons of the vinylphenyl radical, δ 1.08 was obtained (t, I = 7Hz, --CH₂ --B, signal broadened due to partial esterification withmethanol), 2.17 (t, I = 7 Hz, Ar--CH₂ --), H of OH at δ 4.70.

C₁₀ H₁₃ BO₂ (175.2): Calc.: C 68.54; H 7.48; B 6.17; Found: C 68.27; H7.63; B 5.99

D-glyceric acid-(p-vinylanilide)-2,3-O-[2-(p-vinylphenyl)]ethylboranatewas obtained from D-glycericacid-(p-vinylanilide) and2-(p-vinylphenyl)-ethylboricacid in a yield of 48%, MP 79-80° C (frompetroleum ether 60/90) [α]_(D) ²⁰ : +38.0° (c = 1.0, acetone).

C₂₁ H₂₂ BNO₃ (347.2): Calc.: C 72.64; H 6.38; B 3.12; N 4.03; Found: C72.35; H 6.30; B 3.21; N 4.19

Preparation of the Polymer

The polymer was prepared similarly to Example 18. A polymer containingfree aniline groups and β-phenylethylboric acid groups was obtained. Thepolymer had the ability to resolve D,L-glyceric acid.

EXAMPLE 20.

Introduction of β-Phenylethylboric Acid Groups and β-PhenylethylamineGroups by the Polymerization ofD-Glycericacid-[2-(p-vinylphenyl)]-ethylamide-2,3-O-[2-(p-vinylphenyl)]ethylboranate.

Preparation of the Monomer

D-Glycericacid-[2-(p-vinylphenyl)]-ethylamide-2,3-O-2-(p-vinylphenyl)]-ethylboronatewas obtained from D-glycericacid-[2-(p-vinylphenyl)]-ethylamide and2-(p-vinylphenyl)-ethylboric acid in a yield of 90% MP 81° (frompetroleum ether 60/90), [α]_(D) ²⁰ : +15.9° (c = 1.0, acetone).

C₂₈ H₂₆ BNO₃ (375.3): Calc.: C 73.61; H 6.98; B 2.88; N 3.73;

Found: C 73.75; H 7.09; B 2.24; N 3.49

Preparation of the Polymer

This was performed analogously to Example 18. After cleaving off thematrix, a polymer was obtained having free β-phenylethylamine groups andβ-phenylethylboric acid groups. The polymer had an ability to resolveD,L-glyceric acid.

EXAMPLE 21.

Introduction of Optically Active α-Phenylethylamine Groups byPolymerization ofD-Glycericacid-[D-1-(p-vinylphenyl)]-ethylamide-2,3-O-(p-vinylphenyl)-boronate.

Preparation of the Monomer

The amide was prepared analogously to the previously describedpreparation of D-glycericacid-p-vinylanilide from 16 g (0.11 mole) ofD-p-(1-aminoethyl)-styrene and 8.8 g (0.055 mole) of2,3-O-isopropylidene-D-glycericacidmethylester by condensation by theBoudroux method and splitting off the isopropylidene group. An easilycrystallizing substance is obtained, which was then reacted withp-vinylphenylboric acid to form the monomer of the title in good yields.

Preparation of the Polymer

The polymer was prepared analogously to Example 18. After cleaving offthe matrix, a polymer was obtained having phenylboric acid groupings andoptically active D-α-phenylethylamine groupings. The ability to resolveracemates was greatly improved with respect to Examples 1 and 19 by theintroduction of the chiral phenylethylamine group.

EXAMPLE 22

Introduction of an Indenboric Acid Grouping and an Aniline Grouping bythe Polymerization ofD-Glycericacid-(p-vinylanilide)-2,3-0-(6-indenylboronate).

Preparation of the Monommer

6-Indeneboric acid was obtained in the manner described in the case of2-(p-vinylphenyl)-ethylboric acid (Example C 2 ) from 6-boromoindene andtri-n-butylborate, by means of a Grignard reaction. MP 165° (withdecomposition).

This was then reacted with D-glycericacid-(p-vinyl-anilide) to form thedesired monomer.

Preparation of the Polymer

The polymerization of the monomers was performed analogously to Example18. After splitting off the matrix a polymer was obtained having anilinegroupings and indeneboric acid groupings. This boric acid has a poorerconformative mobility than the phenylboric acid grouping. The polymerhad a capacity for the resolution of D,L-glyceric acid.

EXAMPLE 23

Introduction of an Aniline Grouping and of a Boric Acid Grouping WhoseFree Rotation is Impeded. Through the Polymerization ofD-Glycericacid-(P-vinylanilide)-2,3 -O -(4,6-dimethyl-7-indenylboranate).

Preparation of the Monomer

A solution of 127 g (1 mole) of β-chloropropionyl chloride in 70 ml ofmethylene chloride is added drop by drop, with stirring and cooling withan ice bath, to a suspension of 152 g of aluminum chloride in 250 ml ofdistilled methylene chloride. Then, at room temperature, a solution g(180 g (0.97 mole) of 1-bromo-2,4-dimethyl- benzene in 80 ml ofmethylene chloride is added drop by drop. The reaction was completed atroom temperature in 72 hours. The reaction mixture was hydrolyzed onice, the phases were separated, the aqueous ones were again extractedwith methylene chloride, and the combined organic phases were dried overNa₂ SO₄. After concentration of the solvent by evaporation, an oilybrown crude product was obtained, which was purified by distillation.BP₀.2 mm 105.5° C, yield of1-(3-chloropropionyl)-2,4-dimethyl-5-bromobenzene: 230 g (83.5%).

138.4 g (0.5 mole) of this product was added in portions, with stirring,to 400 ml of concentrated sulfuric acid. The reaction mixture wasmaintained for 35 minutes at a temperature of 125° C and then hydrolyzedon ice. The precipitating solid was suction filtered, washed neutralwith water, and then dried in a current of air. The crude product wasrefined by extraction with petroleum ether in a Soxhlet apparatus.

After removal of the solvent by distillation, an orange-colored, powderyproduct is obtained, MP 103° , yield 78.9 g (65.5%) of4-bromo-5,7-dimethylindanone.

The ketone was reduced with 7.1 g of LiAlH₄ in 750 ml of ether. Thesuspension mixture was refluxed for 2-1/2 hours and then hydrolyzed onice. After separation of the phases the aqueous phase was extractedseveral times with ether. The combined ether phases were dried over Na₂SO₄. After concentration, 4-bromo-5,7-dimethylindanole was obtained byrecrystallization from petroleum ether, MP °, yield 43.45 g(93%).

Water is split off from this by heating 20 g (0.0822 mole) with 3 g ofKHSO₄ and 0.1 g of tert. butylcatechol for 15 minutes at 120° .

Refinement by distillation. BP 78° (0.15 Torr), MP 34°,yield 11.5 g(62%) of 7-bromo-4,6-dimethylindene.

From this, 4,6-dimethyl-7-indenylboric acid was obtained in the mannerdescribed in the case of 2-(p-vinylphenyl)- ethylboric acid (Example C2) by reaction to form a Grignard compound, followed by reaction withtri-n-butylborate. This compound was able to be reacted in the usualmanner with D-glycericacid-(p-vinylanilide) to form the desired monomer.

Preparation of the Polymer

The polymerization was performed analogously to Example 18. Aftersplitting off the matrix a polymer was obtained which contained freeindeneboric acid groups and aniline groups. The boric acid was impededin its free rotation and therefore was capaple to a special degree ofachieving a specific orientation of the added-on glyceric acid in thecavity. Its capacity for the resolution of D,L-glyceric acid istherefore particularly good.

EXAMPLE 24.

Transformation of primary amino groups introduced into the polymer totertiary amino groups. In this manner a greater basicity is achieved, onthe one hand, and on the other hand, interaction with a carboxylic acidis limited to an electrostatic one (formation of amides impossible).

Preparation of the Polymer

One gram of each of the amino-group-containing polymers prepared inExamples 1, 4, 5, 18, 19, 20, 21, 22 and 23 was mixed with 7.2 g of 88%formic acid. 10.2 grams of 36% formaldehyde solution was added with icecooling and the mixture was stirred for 30 minutes. Then the mixture wasmelted in the bomb tube under N₂ and the tube was shaken for 24 h at70°. Then the polymer was filtered out, washed with a large amount of1:4 water and methanol mixture, and dried in vacuo at 50° C.

By this method the main part of the free NH₂ groups were transformed to--N(CH₃)₂ groups. The boric acid groupings were preserved. The abilityof the polymers to resolve D,L-glyceric acid was greater than that ofthe starting polymers.

EXAMPLE 25.

Transformation of the Tertiary Amines Introduced into the Polymer toQuaternary Amines. In this manner greater basicity is achieved.

Preparation of the Polymer

One gram of each of the polymers prepared in Example 24 was heated for 6hours at 40° in 10 ml of acetonitrile with 1 ml of CH₃ I under N₂. Inthis manner the quaternary compounds --³⁰ (CH₃)₃ I⁻ were obtained, whichcould be converted with dilute lye to the corresponding hydroxides --³⁰(CH₃)₃ OH⁻. These compounds have a good capacity to resolve D,L-glycericacid.

Introduction of Functional Groups into Polymers by Means of AchiralMatrices EXAMPLE 26.

Introduction of Two Amino Groups at Specific Intervals by Polymerizationof Dicarboxylic Acid Diamides.

Preparation of the Monomers

0.78 g of succinic acid dichloride, for example, was added drop by drop,with vigorous stirring, to a solution of 1.2 g of p-aminostyrene and 3.5ml of distilled pyridine in 400 ml of dry ether. Precipitation tookplace immediately. After 6 h of stirring filtration was performed. Theresidue was carefully washed with dilute HCl , water, NaHCO₃ solution,and again water, and was recrystallized from a large amount of acetone.A 70% yield of succinicacid-di-(p-vinylanilide) was obtained in the formof fine needles melting at 235° with decomposition.

NMR spectrum (DMSO): δ 9.38 (2 H of NH), δ 7.6- 7.2 8 H of the aromatic,6 H of the vinyl group in the form of an AMX spectrum (δ_(A) 5.08, δ_(M)5.62, δ_(X) 6.58, I_(AM) = 1.5 Hz, I_(AX) = 10.5 Hz, I_(MX) = 17 Hz),δ3.25 (4 H of CH₂).

Mass spectrum: m/e 320 ⁺), 119.43.

c₂₀ H₂₀ N₂ O₂ (320): Calc.: C 74.98; H 6.29; N 8.74; Found: C 74.45; H6.21; N 8.60

p-Aminomethylstyrene was also used instead of p-amino-styrene andsuccinic acid di-[(p-vinylphenyl)-methyl]- amide was obtained incrystalline form in this manner.

With these two amine components (p-aminostyrene andp-aminomethylstyrene), the corresponding diamides were prepared from thefollowing acids: oxalic acid, malonic acid, succinic acid, adipic acid,phthalic acid, terephthalic acid, 4,4'-diphenic acid.

Preparation of the Polymers

3 g of the monomer was polymerized in the usual manner with 14 g oftechnical divinylbenzene (55% pure), 200 mg of azoisobutyronitrile and19 ml of acetonitrile. The splitting off of the matrix was performedwith 20% HCl in methanol at 80° C in the bomb tube.

In each case polymers were obtained having free amino groups, two ofthem located at a specific distance from one another. The distancebetween the amino groups is as follows for the derivative of eachparticular acid:

    ______________________________________                                        Oxalic acid         approx. 3.8 A                                             Malonic acid        approx. 4.7 A                                             Succinic acid       approx. 6.0 A                                             Adipic acid         approx. 8.6 A                                             Phthalic acid       approx. 5.4 A                                             Terephthalic acid   approx. 7.2 A                                             4,4'-Diphenic acid  approx. 11.2 A                                            ______________________________________                                    

As in Examples 24 and 25 these primary amino groups were also convertedto tertiary or quaternary amino groups. In the high-pressure fluidchromatography performed with adsorbents on this basis it was found thatthe dicarboxylic acid used as the matrix in each case had higherretention volumes that dicarboxylic acids in which there was a greateror lesser spacing between the functional groups.

EXAMPLE 27

Introduction of Three Amino Groups in a Defined Spatial Relationship toOne Another by Polymerization of Tricarballylic AcidTri-[(p-vinylphenyl)-methyl]-amide.

Preparation of the Monomer

In the manner described in Example 26, tricarballylic acid wastransformed via the acid chloride to the triamide with[(p-vinylphenyl)-methyl]-amine.

Preparation of the Polymer

3 grams of tricarballylicacid-tri-[(p-vinylphenyl)-methyl]-amide werepolymerized in the usual manner with 14 g of technical divinylbenzene(55% pure), 200 mg of azoisobutyronitrile and 19 ml of acetonitrile. Thematrix was split off with 20% HCl in methanol at 80° in the bomb tube.

Polymers were obtained having free amino groups of which three in eachcase were in an established relationship of adjacency to one another.

EXAMPLE 28

Introduction of Two Carboxyl Groups into a Polymer at a SpecificInterval by Polymerization of Diol-di-methacrylates.

Preparation of the Polymer

In each case 1.5 g of the dimethacrylic acid ester of ethyleneglycol, of1,4-butanediol, of 1, 6-hexanediol and of hydroquinone was polymerizedwith 7 g of technical divinylbenzene (55% pure), 100 mg ofazoisobutyronitrile and 8.5 ml of acetonitrile in the usual manner. Thematrix was split off with 20% HCl in methanol at 80° in the bomb tube.The polymers thus prepared contained free carboxyl groups, two of thembeing present in a microcavity at a specific distance from one another.In the high-pressure fluid chromatography using adsorbents on this basisit was found that diamines or diols of the same number of carbon atomsas the matrix have substantially higher retention volumes than those ofa smaller or larger number of carbon atoms.

EXAMPLE 29

Introduction of a Carboxyl Group and of an Amino Group into the Polymerat a Specific Distance From One Another by Polymerizingε-Methacrylaminocapronicacid-[(p-vinylphenyl)-methyl]-amide.

Preparation of the Monomer

8.5 g of methacrylic acid chloride was added drop by drop 10 g ofε-aminocapronic acid methyl ester in the presence of 30 ml of pyridinein 500 ml of ether. After processing in the usual manner (see Example26), easily crystallizing ε-methacrylaminocapronic acid methyl ester wasobtained. By the previously described method of Boudroux (Example 1),this ester was reacted with [(p-vinylphenyl)-methyl]-amine to form themonomer of the title.

Preparation of the Polymer

3 g of the monomer was polymerized in the usual manner with 7 g oftechnical divinylbenzene (55% pure), 100 mg of azoisobutyronitrile and8.5 ml of acetonitrile. The matrix was split off with 20% HCl inmethanol at 80° in the bomb tube.

A polymer was obtained having one amino group and one carboxyl group ina microcavity at a specific distance apart.

Examples of the Introduction of Functional Groups by Means of a Varietyof Chiral Matrix Molecules EXAMPLE 30

Preparation of a Sugar Racemate Resolving Polymer by Polymerization ofMethyl-α-D-mannopyranoside-2,3,4,6-di-(p-vinylphenylboronate)

Preparation of the Monomer

4 g of methyl-α-D-mannopyranoside and 6 g of p-vinylphenylboric acidwere heated in 500 ml of dry dioxane in the presence of 0.1 g oftertiary butylcatechol with slow distillation, until the boilingtemperature of pure dioxane (101° C) was reached (4 hours). Afterconcentration in vacuo, the residue was dissolved in benzene, filteredto remove undissolved substances, and again concentrated.Crystallization from petroleum ether (40/60) gave the monomer of thetitle in colorless crystals, MP 137 -138°,[α]_(D) ²⁵ = 180.6°, [α]₄₃₆ ²⁵= -436.4° (c = 1.0, chloroform).

C₂₄ H₂₄ B₂ O₆ : Calc.: C 66.09; H 5.74; B 5.17; Foud: C 65.57; H 5.79; B4.67

Preparation of the Polymer

The monomer was polymerized by two different method:

(a) 2 g of monomer, 4 ml of ethyleneglycoldimethacrylate, 4 ml ofmethacrylate and 100 mg of azoisobutyronitrile in 8 ml of acetonitrilewere polymerized in the usual manner. The matrix was split off with a4:1 mixture of water and methanol, the cleavage being about 80%complete. The polymer had a racemate resolving ability of α = 1.16 formethyl-α-D,L-mannopyranoside.

(b) In a second batch, 2 g of monomer was polymerized radiochemicallywith 7 g of technical divinylbenzene (55% pure) in 8 ml of acetonitrile.For this purpose the sealed ampoule was exposed for 6 hours to aradiation of 1 × 10⁸ rads from a cobalt-60 source of 16,000 Curies. Inthis manner, polymerization, chemical cross-linking and additionalradiochemical crosslinking of the reaction mixture was accomplished. Amechanically very stable, macroporous polymer was obtained which, afterthe splitting off of the matrix, had a very good racemate resolvingability.

EXAMPLE 31

Introduction of Three Different Functional Groups by the PolymerizationofN-(p-vinylbenzylidene)-3',4'-dihydroxy-L-phenylalanine-(p-vinylanilide)-3',4'-O-(6-indenylboranate).

Preparation of the Monomer

1 gram of 3',4'-di-O-trifluoracetoxy-N-trifluoroacetyl-L-phenylalaninewas converted to the acid chloride with 10 ml of thionyl chloride, and,after the excess SO₂ Cl₂ had been distilled off, was dissolved in 20 mlof benzene. To this solution of 1.2 g of p-aminostyrene in 20 ml ofbenzene was slowly added, drop by drop. A white precipitate settled out.The mixture was refluxed for one more hour and the solvent was removedby distillation at reduced pressure. The crude product was washedcarefully with water several times and then recrystallized from aqueousethanol solution. The3',4'-di-O-trifluoracetoxy-N-trifluoracetyl-L-phenylalanine-(p-vinylanilide)was obtained in colorless crystals.

Then the trifluoracetyl radicals were split off by allowing 1 g of theproduct to stand for 48 hours in 50 ml of 0.2N NaOH in 90% ethanol. Thisreaction was performed under nitrogen gas with stirring. Afterneutralization of the solution it was concentrated and the residue wasrecrystallized.

1 gram of 3',4'-dihydroxy-L-phenylalanine-(p-vinylanilide) was suspendedin 10 ml of 2N NaOH and chilled to 0° C. 1.5 g of p-vinylbenzaldehydewas slowly added, drop by drop, with stirring. After 6 hours ofstirring, the newly formed precipitate was removed by filtration andrefined by recrystallization, to produce a good yield of N-(p-vinylbenzylidene)-3',4'-dihydroxy-L-phenylalanine-(p-vinylanilide).

1 gram of this compound was dissolved in 300 ml of dioxane and warmedunder a weak vacuum with 360 mg of 6-indenylboric acid such that thesolution boiled weakly at 45° C and the water that formed was withdrawnazeotropically. Then the mixture was concentrated and the concentratewas recrystallized to produce the monomer of the title.

Preparation of the Polymer

2 grams of the above-described polymer polymer were polymerized with 7grams of technical divinylbenzene (55% pure) and 100 mg ofazoisobutyronitrile in 9.5 ml of acetonitrile, in the usual manner. Thematrix was split off with 20% methanolic HCl at 100° C in the bomb tube.A polymer was obtained having microcavities which contained one freeamino, aldehyde and boric acid grouping each.

The polymer had a very good ability to resolve3',4'-dihydroxy-D,L-phenylalanine.

It is to be realized that the above examples exemplify the invention andare not intended to be limitative as one can substitute for theD-glyceric acid, another optically active organic compound. Similarly,for each of the polymerizable residues bonded to such D-glyceric acidthere can be substituted another polymerizable or polycondensableresidue.

What is claimed is:
 1. A method of separating an optically activeantipode from a racemate thereof which comprises contacting saidracemate with a three-dimensional polymeric material comprising apolymer of an olefinically unsaturated compound or a polycondensationpolymer having in its physical configuration a void whose size and shapeand the arrangement of the functional groups therein correspond to thesize and shape and the arrangement of the functional groups of anoptically active compound, said polymeric material being operative topreferentially sorb an optically active compound whose size and shapecorrespond to said void when a racemate mixture thereof is passed overthe three-dimensional polymeric material wherein the void of suchpolymeric material corresponds to the size and shape of the opticallyactive antipode to be separated from said racemate.
 2. Method accordingto claim 1 wherein said racemate is DL-glycericacid and the void in saidpolymeric material corresponds in size and shape to D-glycericacid. 3.Method according to claim 1 wherein the racemate is D-L-glycericacidmethylester and the void in said polymeric material corresponds in sizeand shape to D-glycericacid.
 4. Method according to claim 1 wherein theracemate is D-L-glycericaldehyde and the void in the said polymericmaterial corresponds in size and shape to D-glycericacid.
 5. Methodaccording to claim 1 wherein the racemate is D-L-mannitol and the voidin the polymeric material corresponds in size and shape to D-mannitol.